3-148997054-TTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr3-148997054-T-TTGTGTGTG
• rs10571382
• NM_004130.4:c.481+172_481+179dupGTGTGTGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004130.4(GYG1):​c.481+172_481+179dupGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 606,362 control chromosomes in the GnomAD database, including 105 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (73 hom., cov: 0)
  • Exomes 𝑓: 0.019 (32 hom.)
• Consequence: GYG1 NM_004130.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.285
• Publications: 1 publications found

Genes affected

GYG1 (HGNC:4699): (glycogenin 1) This gene encodes a member of the glycogenin family. Glycogenin is a glycosyltransferase that catalyzes the formation of a short glucose polymer from uridine diphosphate glucose in an autoglucosylation reaction. This reaction is followed by elongation and branching of the polymer, catalyzed by glycogen synthase and branching enzyme, to form glycogen. This gene is expressed in muscle and other tissues. Mutations in this gene result in glycogen storage disease XV. This gene has pseudogenes on chromosomes 1, 8 and 13 respectively. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

GYG1 Gene-Disease associations (from GenCC):

• polyglucosan body myopathy type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, PanelApp Australia, ClinGen
• glycogen storage disease XV

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-148997054-T-TTGTGTGTG is Benign according to our data. Variant chr3-148997054-T-TTGTGTGTG is described in ClinVar as Likely_benign. ClinVar VariationId is 1196791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0276 (4137/149796) while in subpopulation AFR AF = 0.0408 (1656/40614). AF 95% confidence interval is 0.0391. There are 73 homozygotes in GnomAd4. There are 2071 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 73 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004130.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	NM_004130.4	MANE Select	c.481+172_481+179dupGTGTGTGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+172_481+179dupGTGTGTGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+172_481+179dupGTGTGTGT		intron	N/A	NP_001171650.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	ENST00000345003.9	TSL:1 MANE Select	c.481+150_481+151insTGTGTGTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+150_481+151insTGTGTGTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+150_481+151insTGTGTGTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4130 AN: 149680 Hom.: 72 Cov.: 0

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.0299

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0250

GnomAD4 exome AF: 0.0194 AC: 8861 AN: 456566 Hom.: 32 AF XY: 0.0199 AC XY: 4843 AN XY: 243632

African (AFR) AF: 0.0343 AC: 440 AN: 12836

American (AMR) AF: 0.0134 AC: 322 AN: 24082

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 172 AN: 14698

East Asian (EAS) AF: 0.00 AC: 0 AN: 28888

South Asian (SAS) AF: 0.0300 AC: 1496 AN: 49926

European-Finnish (FIN) AF: 0.0217 AC: 626 AN: 28814

Middle Eastern (MID) AF: 0.0219 AC: 46 AN: 2104

European-Non Finnish (NFE) AF: 0.0195 AC: 5251 AN: 269326

Other (OTH) AF: 0.0196 AC: 508 AN: 25892

GnomAD4 genome AF: 0.0276 AC: 4137 AN: 149796 Hom.: 73 Cov.: 0 AF XY: 0.0283 AC XY: 2071 AN XY: 73086

African (AFR) AF: 0.0408 AC: 1656 AN: 40614

American (AMR) AF: 0.0196 AC: 295 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 73 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.0369 AC: 174 AN: 4716

European-Finnish (FIN) AF: 0.0227 AC: 231 AN: 10178

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0241 AC: 1625 AN: 67414

Other (OTH) AF: 0.0247 AC: 51 AN: 2062

Alfa AF: 0.0182 Hom.: 193

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10571382; hg19: chr3-148714841;